Phosphorus oxychloride → 4-Chloro-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidine

HRID 1517438Notes

Reaction equation

HRID 1517438 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]=[CH:13][NH:14][C:15](=O)[C:16]=3[N:17]=2)=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.P(Cl)(Cl)([Cl:30])=O>C1(C)C=CC=CC=1>[Cl:30][C:15]1[C:16]2[N:17]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[CH:9]=[CH:10][C:11]=2[N:12]=[CH:13][N:14]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 1360008906-(4-Fluorophenyl)pyrido[3,2-d]pyrimidin-4(1H)-one

Product 1

HCID 579067564-Chloro-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidineYield 96.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a mixture of 6-(4-fluorophenyl)-pyrido[3,2-d]-pyrimidin-4(3H)one (482 mg, 2 mmol) in toluene (20 ml), was added diisopropylethylamine (1.0 ml, 6 mmol) and phosphorus oxychloride (0.56 ml, 6 mmol). The reaction mixture was refluxed for 1 hour. After concentration under reduced pressure, the residue was extracted with dichloromethane (100 ml), and washed with ice water till pH 6-7. The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure yielding the title compound as a yellowish solid (0.50 g, yield 96%) which was characterised as follows: Rf=0.90 (MeOH/CH2Cl2=1/9).

Workup

  1. temperatureThe reaction mixture was refluxed for 1 hour
  2. concentrationAfter concentration under reduced pressure
  3. extractionthe residue was extracted with dichloromethane (100 ml)
  4. washwashed with ice water till pH 6-7
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-74101667e78a4a88a39bbf8ce3da0730
Source dataset
uspto-grants-2012_07
Patent number
US08232278B2

Reaction notes

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